Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVTBNSM)

• DOT Name: Glycerate kinase (GLYCTK)
• Synonyms: EC 2.7.1.31; HBeAg-binding protein 4
• Gene Name: GLYCTK
• Related Disease:
  D-glyceric aciduria
  Primary hyperoxaluria type 2
  Schizophrenia
• UniProt ID: GLCTK_HUMAN
• EC Number: 2.7.1.31
• Pfam ID: PF13660 ; PF05161
• Sequence:
  MAAALQVLPRLARAPLHPLLWRGSVARLASSMALAEQARQLFESAVGAVLPGPMLHRALS
  LDPGGRQLKVRDRNFQLRQNLYLVGFGKAVLGMAAAAEELLGQHLVQGVISVPKGIRAAM
  ERAGKQEMLLKPHSRVQVFEGAEDNLPDRDALRAALAIQQLAEGLTADDLLLVLISGGGS
  ALLPAPIPPVTLEEKQTLTRLLAARGATIQELNTIRKALSQLKGGGLAQAAYPAQVVSLI
  LSDVVGDPVEVIASGPTVASSHNVQDCLHILNRYGLRAALPRSVKTVLSRADSDPHGPHT
  CGHVLNVIIGSNVLALAEAQRQAEALGYQAVVLSAAMQGDVKSMAQFYGLLAHVARTRLT
  PSMAGASVEEDAQLHELAAELQIPDLQLEEALETMAWGRGPVCLLAGGEPTVQLQGSGRG
  GRNQELALRVGAELRRWPLGPIDVLFLSGGTDGQDGPTEAAGAWVTPELASQAAAEGLDI
  ATFLAHNDSHTFFCCLQGGAHLLHTGMTGTNVMDTHLLFLRPR
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Glycine, serine and threonine metabolism (hsa00260)
  Glycerolipid metabolism (hsa00561)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
• Reactome Pathway: Fructose catabolism (R-HSA-70350)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
D-glyceric aciduria	DIS0DL0F	Strong	Autosomal recessive	[1]
Primary hyperoxaluria type 2	DISGZT3W	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[3]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Glycerate kinase (GLYCTK).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycerate kinase (GLYCTK).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glycerate kinase (GLYCTK).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glycerate kinase (GLYCTK).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glycerate kinase (GLYCTK).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glycerate kinase (GLYCTK).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glycerate kinase (GLYCTK).	[8]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Glycerate kinase (GLYCTK).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycerate kinase (GLYCTK).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glycerate kinase (GLYCTK).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Glycerate kinase (GLYCTK).	[13]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Glycerate kinase (GLYCTK).	[10]

References

• [1] D-glyceric aciduria is caused by genetic deficiency of D-glycerate kinase (GLYCTK). Hum Mutat. 2010 Dec;31(12):1280-5. doi: 10.1002/humu.21375. Epub 2010 Nov 9.
• [2] d-Glyceric aciduria does not cause nonketotic hyperglycinemia: A historic co-occurrence.Mol Genet Metab. 2017 Jun;121(2):80-82. doi: 10.1016/j.ymgme.2017.04.009. Epub 2017 Apr 20.
• [3] Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.Hum Brain Mapp. 2018 Nov;39(11):4183-4195. doi: 10.1002/hbm.24238. Epub 2018 Jun 26.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.